RESUMO
PURPOSE: To assess the efficacy and safety of concurrent hypofractionated radiotherapy plus anti-PD-1 antibody and SOX chemotherapy in the treatment of metastatic pancreatic cancer (mPC) after failure of first-line chemotherapy. METHODS: Patients with pathologically confirmed mPC who failed standard first-line chemotherapy were enrolled. The patients were treated with a regimen of hypofractionated radiotherapy, SOX chemotherapy, and immune checkpoint inhibitors at our institution. We collected the patients' clinical information and outcome measurements. The median progression-free survival (mPFS) was the primary endpoint of the study, followed by disease control rate (DCR), objective response rate (ORR), median overall survival (mOS) and safety. Exploratory analyses included biomarkers related to the benefits. RESULTS: Between February 24, 2021, and August 30, 2023, twenty-five patients were enrolled in the study, and twenty-three patients who received at least one dose of the study agent had objective efficacy evaluation. The mPFS was 5.48 months, the mOS was 6.57 months, and the DCR and ORR were 69.5% and 30.4%, respectively. Among the seven patients who achieved a PR, the median duration of the response was 7.41 months. On-treatment decreased serum CA19-9 levels were associated with better overall survival. Besides, pretreatment inflammatory markers were associated with tumor response and survival. CONCLUSIONS: Clinically meaningful antitumor activity and favorable safety profiles were demonstrated after treatment with these combination therapies in patients with refractory mPC. On-treatment decreased serum CA19-9 levels and pretreatment inflammatory markers platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), lactate dehydrogenase (LDH) might be biomarkers related to clinical benefits. CLINICAL TRIAL REGISTRATION: https://www.chictr.org.cn/showproj.html?proj=130211 , identifier: ChiCTR2100049799, date of registration: 2021-08-09.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias Pancreáticas , Hipofracionamento da Dose de Radiação , Humanos , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/radioterapia , Neoplasias Pancreáticas/terapia , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Adulto , Inibidores de Checkpoint Imunológico/uso terapêutico , Ácido Oxônico/uso terapêutico , Ácido Oxônico/administração & dosagem , Quimiorradioterapia/métodos , Tegafur/uso terapêutico , Tegafur/administração & dosagem , Gencitabina , Metástase NeoplásicaRESUMO
INTRODUCTION: Although histological subtype in lung adenocarcinoma has been reported as a poor prognostic factor in several studies, its utility has not yet been revealed as an adaptation criterion of postoperative adjuvant chemotherapy. METHODS: Four hundred ninety-four lung adenocarcinoma patients were enrolled in this retrospective study. A subanalysis was performed in 420 lung adenocarcinoma patients with pathological stage 0-I disease for risk factors of postoperative recurrence. RESULTS: Maximum standardized uptake value (SUVmax) (p < 0.01), pathological stage ≥II (p < 0.04), and adjuvant chemotherapy (p < 0.01) were risk factors for recurrence in the multivariate analysis, whereas histological subtype was not a significant factor for recurrence at all stages. In the subanalysis, univariate analysis showed that carcinoembryonic antigen expression (p < 0.01), prognostic nutrition index (p = 0.03), SUVmax (p < 0.01), lymphatic invasion (p < 0.01), vascular invasion (p < 0.01), grade 3-4 differentiation (p < 0.01), pathological stage ≥IA3 (p < 0.01), and histological subtype (p = 0.03) were significant risk factors of recurrence. SUVmax (p < 0.01) was the only risk factor for recurrence in the multivariate analysis, whereas histological subtype was not (p = 0.07). Relapse-free survival (RFS) was significantly worse in the micropapillary- and solid-predominant subtype groups than in the other subtypes (p = 0.01). On the other hand, RFS with or without uracil-tegafur as adjuvant chemotherapy in lung micropapillary- or solid-predominant adenocarcinoma patients with pathological stage IA-IB disease was not significantly different. CONCLUSION: This study suggested that histological subtypes, such as micropapillary- or solid-predominant pattern, are risk factors for recurrence in pathological stage 0-I lung adenocarcinoma and may be necessary adjuvant chemotherapy instead of uracil-tegafur.
Assuntos
Adenocarcinoma de Pulmão , Neoplasias Pulmonares , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Tegafur/uso terapêutico , Estudos Retrospectivos , Estadiamento de Neoplasias , Recidiva Local de Neoplasia/patologia , Adenocarcinoma de Pulmão/patologia , PrognósticoRESUMO
OBJECTIVE: This study aims to develop a nomogram integrating inflammation (NLR), Prognostic Nutritional Index (PNI), and EBV DNA (tumor burden) to achieve personalized treatment and prediction for stage IVA NPC. Furthermore, it endeavors to pinpoint specific subgroups that may derive significant benefits from S-1 adjuvant chemotherapy. METHODS: A total of 834 patients diagnosed with stage IVA NPC were enrolled in this study and randomly allocated into training and validation cohorts. Multivariate Cox analyses were conducted to identify independent prognostic factors for constructing the nomogram. The predictive and clinical utility of the nomogram was assessed through measures including the AUC, calibration curve, DCA, and C-indexes. IPTW was employed to balance baseline characteristics across the population. Kaplan-Meier analysis and log-rank tests were utilized to evaluate the prognostic value. RESULTS: In our study, we examined the clinical features of 557 individuals from the training cohort and 277 from the validation cohort. The median follow-up period was 50.1 and 49.7 months, respectively. For the overall cohort, the median follow-up duration was 53.8 months. The training and validation sets showed 3-year OS rates of 87.7% and 82.5%, respectively. Meanwhile, the 3-year DMFS rates were 95.9% and 84.3%, respectively. We created a nomogram that combined PNI, NRI, and EBV DNA, resulting in high prediction accuracy. Risk stratification demonstrated substantial variations in DMFS and OS between the high and low risk groups. Patients in the high-risk group benefited significantly from the IC + CCRT + S-1 treatment. In contrast, IC + CCRT demonstrated non-inferior 3-year DMFS and OS compared to IC + CCRT + S-1 in the low-risk population, indicating the possibility of reducing treatment intensity. CONCLUSIONS: In conclusion, our nomogram integrating NLR, PNI, and EBV DNA offers precise prognostication for stage IVA NPC. S-1 adjuvant chemotherapy provides notable benefits for high-risk patients, while treatment intensity reduction may be feasible for low-risk individuals.
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Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas , Estadiamento de Neoplasias , Nomogramas , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Carcinoma Nasofaríngeo/tratamento farmacológico , Carcinoma Nasofaríngeo/mortalidade , Carcinoma Nasofaríngeo/patologia , Quimioterapia Adjuvante/métodos , Prognóstico , Neoplasias Nasofaríngeas/tratamento farmacológico , Neoplasias Nasofaríngeas/mortalidade , Neoplasias Nasofaríngeas/patologia , Inflamação , Adulto , Avaliação Nutricional , Herpesvirus Humano 4/isolamento & purificação , Tegafur/uso terapêutico , Tegafur/administração & dosagem , DNA Viral , Combinação de Medicamentos , Ácido Oxônico/uso terapêutico , Ácido Oxônico/administração & dosagem , Idoso , Estimativa de Kaplan-MeierRESUMO
BACKGROUND/OBJECTIVES: Liposomal irinotecan plus 5-fluorouracil and leucovorin (nal-IRI + 5-FU/LV) provides survival benefits for metastatic pancreatic adenocarcinoma (mPDAC) refractory to gemcitabine-based treatment, mainly gemcitabine plus nab-paclitaxel (GA), in current practice. Gemcitabine plus S-1 (GS) is another commonly administered first-line regimen before nab-paclitaxel reimbursement; however, the efficacy and safety of nal-IRI + 5-FU/LV for mPDAC after failed GS treatment has not been reported and was therefore explored in this study. METHODS: In total, 177 patients with mPDAC received first-line GS or GA treatment, followed by second-line nal-IRI + 5-FU/LV treatment (identified from a multicenter retrospective cohort in Taiwan from 2018 to 2020); 85 and 92 patients were allocated to the GS and GA groups, respectively. Overall survival (OS), time-to-treatment failure (TTF), and adverse events were compared between the two groups. RESULTS: The baseline characteristics of the two groups were generally similar; however, a higher median age (67 versus 62 years, p < 0.001) and fewer liver metastases (52% versus 78%, p < 0.001) were observed in the GS versus GA group. The median OS was 15.0 and 15.9 months in the GS and GA groups, respectively (p = 0.58). The TTF (3.1 versus 2.8 months, p = 0.36) and OS (7.6 versus 6.7 months, p = 0.83) after nal-IRI treatment were similar between the two groups. More patients in the GS group developed mucositis during nal-IRI treatment (15% versus 4%, p = 0.02). CONCLUSIONS: The efficacy of second-line nal-IRI +5-FU/LV treatment was unaffected by prior S-1 exposure. GS followed by nal-IRI treatment is an alternative treatment sequence for patients with mPDAC.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Combinação de Medicamentos , Fluoruracila , Irinotecano , Leucovorina , Ácido Oxônico , Neoplasias Pancreáticas , Tegafur , Humanos , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/patologia , Leucovorina/uso terapêutico , Leucovorina/administração & dosagem , Pessoa de Meia-Idade , Masculino , Feminino , Fluoruracila/uso terapêutico , Fluoruracila/administração & dosagem , Idoso , Irinotecano/uso terapêutico , Irinotecano/administração & dosagem , Tegafur/administração & dosagem , Tegafur/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Estudos Retrospectivos , Ácido Oxônico/administração & dosagem , Ácido Oxônico/uso terapêutico , Lipossomos , Resultado do Tratamento , Metástase Neoplásica , Adulto , Paclitaxel/administração & dosagem , Paclitaxel/uso terapêuticoRESUMO
BACKGROUND: Microsatellite instability-high (MSI-H) tumors are distinct molecular subtypes in gastric cancer. However, a few studies have comprehensively reported the molecular features of MSI-H tumors and their prognostic factors in locally advanced gastric cancer. This study aimed to clarify the molecular features and prognostic factors of locally advanced MSI-H gastric cancer. METHODS: This study included 499 patients with locally advanced gastric cancer who underwent radical gastrectomy. We evaluated the MSI status and compared with previously published whole-exome sequencing, panel sequencing, and gene expression profiling data. Clinicopathological characteristics and molecular profiles were compared between patients with MSI-H and microsatellite stable (MSS) gastric cancer. A subgroup analysis of survival was performed in patients with MSI-H gastric cancer. RESULTS: MSI-H tumors were detected in 79 of 499 patients (15.8%). MSI-H tumors were associated with an increased tumor mutational burden, MLH1 downregulation, CD274 (PD-L1) upregulation, and enrichment of cell cycle pathways. Among patients with MSI-H gastric cancer, the disease-specific survival (DSS) tended to be better in the surgery plus tegafur, gimeracil, and oteracil potassium (S-1) adjuvant chemotherapy group than in the surgery alone group, especially for stage III patients. Furthermore, DSS was better in the T cell-inflamed gene expression signature-high group, and it tended to be worse in the non-solid type poorly differentiated adenocarcinoma group. CONCLUSIONS: The molecular features and prognostic factors of locally advanced MSI-H gastric cancer were clarified. S-1 adjuvant chemotherapy appears to be beneficial, and the T cell-inflamed gene expression signature and histopathological type are prognostic factors in MSI-H tumors.
Assuntos
Gastrectomia , Instabilidade de Microssatélites , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/genética , Neoplasias Gástricas/patologia , Neoplasias Gástricas/mortalidade , Feminino , Masculino , Prognóstico , Idoso , Pessoa de Meia-Idade , Biomarcadores Tumorais/genética , Tegafur/uso terapêutico , Adulto , Combinação de Medicamentos , Ácido Oxônico/uso terapêutico , Idoso de 80 Anos ou mais , Antígeno B7-H1/genética , Antígeno B7-H1/metabolismo , Taxa de Sobrevida , Mutação , Perfilação da Expressão Gênica , Sequenciamento do Exoma , Proteína 1 Homóloga a MutL/genética , Regulação Neoplásica da Expressão GênicaRESUMO
BACKGROUND: This study examined temporal shifts in adjuvant therapy patterns in Japanese patients with resectable gastric cancer (GC) and treatment patterns of first-line and subsequent therapy among those with recurrent disease. METHODS: This retrospective analysis of hospital-based administrative claims data (April 1, 2008 to March 31, 2022) included adults (aged ≥ 20 years) with GC who started adjuvant therapy on or after October 1, 2008 (adjuvant cohort) and patients in the adjuvant cohort with disease recurrence (recurrent cohort), further defined by the time to recurrence (≤ 180 or > 180 days after adjuvant therapy). RESULTS: In the adjuvant cohort (n = 17,062), the most common regimen during October 2008-May 2016 was tegafur/gimeracil/oteracil potassium (S-1; 95.7%). As new standard adjuvant regimen options were established, adjuvant S-1 use decreased to 65.0% and fluoropyrimidine plus oxaliplatin or docetaxel plus S-1 use increased to 15.0% and 20.0%, respectively, in September 2019-March 2022. In the recurrent cohort with no history of trastuzumab/trastuzumab deruxtecan treatment (n = 1257), the most common first-line regimens were paclitaxel plus ramucirumab (34.0%), capecitabine plus oxaliplatin (CapeOX; 17.0%), and nab-paclitaxel plus ramucirumab (10.1%) in patients with early recurrence, and S-1 plus oxaliplatin (26.3%), S-1 plus cisplatin (15.3%), CapeOX (14.0%), S-1 (13.2%), and paclitaxel plus ramucirumab (10.8%) in those with late recurrence. CONCLUSIONS: This study demonstrated temporal shifts in adjuvant treatment patterns that followed the establishment of novel regimens, and confirmed that post-recurrent treatment patterns were consistent with the Japanese Gastric Cancer Association guideline recommendations.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Recidiva Local de Neoplasia , Neoplasias Gástricas , Tegafur , Humanos , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/cirurgia , Neoplasias Gástricas/patologia , Neoplasias Gástricas/terapia , Feminino , Masculino , Estudos Retrospectivos , Pessoa de Meia-Idade , Idoso , Japão , Quimioterapia Adjuvante , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/patologia , Tegafur/administração & dosagem , Tegafur/uso terapêutico , Adulto , Ácido Oxônico/administração & dosagem , Ácido Oxônico/uso terapêutico , Combinação de Medicamentos , Bases de Dados Factuais , Estudos de Coortes , Oxaliplatina/administração & dosagem , Oxaliplatina/uso terapêutico , Adulto Jovem , Idoso de 80 Anos ou mais , PiridinasRESUMO
OBJECTIVES: To investigate temporal trends in treatment patterns and prognostic factors for overall survival in patients with metastatic biliary tract cancer. METHODS: From the Tokushukai REAl-world Data project, we identified 945 patients with metastatic biliary tract cancer treated with gemcitabine, tegafur/gimeracil/oteracil, gemcitabine plus cisplatin, gemcitabine plus tegafur/gimeracil/oteracil or gemcitabine plus cisplatin and tegafur/gimeracil/oteracil between April 2010 and March 2022. Stratified/conventional Cox regression analyses were conducted to examine the association between overall survival and patient- and tumour-related factors, study period, hospital volume, hospital type and first-line chemotherapy regimen. Using inverse probability of treatment weighting with propensity scores, overall survival was also compared between monotherapy and combination therapy groups. RESULTS: We enrolled 366 patients (199 men; median age, 72 years). Over a median follow-up of 5.2 months, the median overall survival was 7.0 months (95% confidence interval 6.2-9.0), and the median time to treatment failure was 3.5 months (95% confidence interval 3.1-4.5). Median overall survival and time to treatment failure for gemcitabine/tegafur-gimeracil-oteracil/gemcitabine plus cisplatin/gemcitabine plus tegafur-gimeracil-oteracil/gemcitabine plus cisplatin and tegafur-gimeracil-oteracil regimen were 6.2/6.6/7.9/16.2/15.1 and 2.8/3.4/4.1/15.3/7.4 months, respectively. Primary disease site, previous surgery, previous endoscopic procedures and hospital type were identified as significant prognostic factors. Inverse probability of treatment weighting analysis demonstrated that combination therapy had a significantly better prognosis than monotherapy (hazard ratio 0.61, 95% confidence interval 0.43-0.88, P = 0.006). CONCLUSIONS: Our real-world data analysis showed that standard care for metastatic biliary tract cancer is widely used in hospitals throughout Japan and verified the survival benefits of combination therapy over monotherapy observed in prior clinical trials. CLINICAL TRIAL NUMBER: UMIN000050590 (http://www.umin.ac.jp/ctr/index.htm).
Assuntos
Neoplasias dos Ductos Biliares , Neoplasias do Sistema Biliar , Idoso , Feminino , Humanos , Masculino , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias do Sistema Biliar/tratamento farmacológico , Neoplasias do Sistema Biliar/patologia , Cisplatino/uso terapêutico , Gencitabina , Japão , Ácido Oxônico/uso terapêutico , Tegafur/uso terapêutico , Resultado do TratamentoRESUMO
BACKGROUND: The aim of this study was to explore the clinical utility of serum HER2 extracellular domain (sHER2 ECD) using data from a clinical trial evaluating trastuzumab combined S-1 plus oxaliplatin (SOX) in HER2 positive gastric cancer. METHODS: sHER2 ECD were prospectively measured at baseline and subsequent treatment courses. Based on each quantile point of baseline sHER2 ECD levels and its early changes, patients were divided into two groups and compared clinical outcomes. RESULTS: 43 patients were enrolled, and 17 patients (39.5%) were positive for baseline sHER2 ECD. Higher baseline sHER2 ECD levels tended to have lower hazard ratios (HRs). When divided into two groups by baseline sHER2 ECD of 19.1 ng/ml, median progression-free survival (PFS) and overall survival (OS) was longer in the higher group (mPFS: 16.8 vs 8.7 months, p = 0.359. mOS: 35.5 vs 20.6 months, p = 0.270), respectively. After initiation of treatment, sHER2 ECD significantly decreased up until the third cycle. Higher reduction rates of sHER2 ECD within 3 cycles also tended to have lower HRs. When divided into two groups by reduction rate of 42.5%, mPFS and mOS was longer in the higher reduced group (mPFS: 17.2 vs 8.7 months, p = 0.095. mOS: 65.0 vs 17.8 months, p = 0.047), respectively. Furthermore, higher reduction rates could surrogate higher objective response rates (ORR) (ORR: 90% vs 63.2% for 29.5%, p = 0.065. 100% vs 70% for 42.5%, p = 0.085), respectively. CONCLUSIONS: Baseline sHER2 ECD levels and its early decline may be useful biomarkers for SOX plus trastuzumab efficacy in HER2 positive gastric cancer.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Combinação de Medicamentos , Oxaliplatina , Ácido Oxônico , Receptor ErbB-2 , Neoplasias Gástricas , Tegafur , Trastuzumab , Humanos , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/sangue , Feminino , Receptor ErbB-2/sangue , Trastuzumab/uso terapêutico , Trastuzumab/administração & dosagem , Masculino , Pessoa de Meia-Idade , Ácido Oxônico/administração & dosagem , Ácido Oxônico/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Idoso , Oxaliplatina/uso terapêutico , Oxaliplatina/administração & dosagem , Tegafur/administração & dosagem , Tegafur/uso terapêutico , Adulto , Estudos Prospectivos , Biomarcadores Tumorais/sangue , Intervalo Livre de ProgressãoRESUMO
This patient visited our hospital for the purpose of detailed examination of prostate cancer in his seventies. Abdominal contrast-enhanced computed tomography(CT)revealed a low-density mass of 2 cm in the pancreatic head. He was diagnosed with pancreatic cancer. Pancreaticoduodenectomy was performed after 2 courses of gemcitabine and S-1 therapy were performed as neoadjuvant chemotherapy. An intraoperative clamp test of the gastroduodenal artery showed that the pulsation of the common hepatic artery and the proper hepatic artery was weak but sufficient, so the gastroduodenal artery was cut and the operation was completed as planned. A blood test on the 1st day after the operation showed elevated levels of AST 537 U/L, ALT 616 U/L, and 7 hours later blood sampling showed further increases in AST 1,455 U/L, ALT 1,314 U/L. After a detailed review of the preoperative CT, celiac artery stenosis due to compression of the arcuate ligament was suspected, and urgent median arcuate ligament release was performed on the same day. Dissection of the arcuate ligament significantly improved the pulsation of the common hepatic artery and proper hepatic artery. Postoperatively, hepatic enzymes improved and ISGPS showed Grade B pancreatic juice leakage, but the patient was discharged from the hospital on the 49th postoperative day without any other complications. He took S-1 as adjuvant chemotherapy, and no signs of recurrence have been observed 9 months after the operation.
Assuntos
Adenocarcinoma , Artéria Celíaca , Neoplasias Pancreáticas , Pancreaticoduodenectomia , Humanos , Adenocarcinoma/cirurgia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Artéria Celíaca/cirurgia , Constrição Patológica/cirurgia , Desoxicitidina/análogos & derivados , Desoxicitidina/uso terapêutico , Desoxicitidina/administração & dosagem , Combinação de Medicamentos , Gencitabina , Síndrome do Ligamento Arqueado Mediano/cirurgia , Ácido Oxônico/uso terapêutico , Ácido Oxônico/administração & dosagem , Neoplasias Pancreáticas/cirurgia , Tegafur/uso terapêutico , Tegafur/administração & dosagemRESUMO
BACKGROUND: Based on the Japan Adjuvant Study Group of Pancreatic Cancer 01 study, the standard duration of adjuvant chemotherapy with S-1 (an oral 5-fluorouracil prodrug consisting of tegafur, gimeracil, and oteracil) in patients with resected pancreatic ductal adenocarcinoma (PDAC) was considered to be 6 months, but the impact of increasing its duration on postoperative survival was unknown. Here, the authors investigated this question by reviewing real-world data from a large cohort of patients with PDAC. METHODS: In total, 3949 patients who underwent surgery for PDAC during the study period followed by S-1 adjuvant chemotherapy in board-certified institutions were included. Based on the duration of S-1 chemotherapy, two subgroups were defined: a standard-duration group that included patients who were treated for 180 ± 30 days and a longer duration group that included patients who received treatment for >210 days. RESULTS: The median duration of S-1 chemotherapy was 167 days, with a mean ± standard deviation of 200 ± 193 days. After excluding patients who had a recurrence within 210 days after the initiation of adjuvant chemotherapy, postoperative recurrence-free survival (RFS) and overall survival (OS) in the standard-duration group (n = 1473) and the longer duration group (n = 975) were compared. RFS and OS did not differ significantly between the standard-duration and longer duration groups (5-year RFS: 37.8% vs. 36.2% respectively; p = .6186; 5-year OS: 52.8% vs. 53.4%, respectively; p = .5850). The insignificant difference was verified by multivariate analysis and propensity-score matching analysis. CONCLUSIONS: The current findings suggest that extending S-1 adjuvant chemotherapy beyond 6 months has no significant additional effect on survival in patients with PDAC. This could be useful in determining whether to extend S-1 chemotherapy in patients who have completed the standard 6-month treatment.
Assuntos
Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Humanos , Tegafur/uso terapêutico , Ácido Oxônico/uso terapêutico , Japão/epidemiologia , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/cirurgia , Neoplasias Pancreáticas/patologia , Quimioterapia Adjuvante , Carcinoma Ductal Pancreático/tratamento farmacológico , Carcinoma Ductal Pancreático/cirurgia , Carcinoma Ductal Pancreático/patologia , Pâncreas/patologia , Estudos Retrospectivos , Neoplasias PancreáticasRESUMO
BACKGROUND: S-1 plus docetaxel (DS) therapy followed by S-1 is the standard of care in Japan in postoperative adjuvant chemotherapy for stage III gastric cancer, but long-term survival and the number of DS cycles required are unclear. The purpose of this study was to investigate the impact of the number of cycles of DS therapy on the 5-year survival in stage III gastric cancer in a pooled analysis of two phase II trials (OGSG0604 and OGSG1002). PATIENTS AND METHODS: Patients with histologically confirmed stage III gastric cancer who underwent gastrectomy with D2 lymphadenectomy were enrolled in this pooled analysis. They received DS therapy for four or eight cycles, followed by S-1 until 1 year postgastrectomy. The 5-year overall survival (OS) and the 5-year disease free survival (DFS) by the landmark analysis was evaluated. RESULTS: In total, 113 patients from the OGSG0604 and OGSG1002 trials were enrolled in this study. The landmark analysis showed a 5-year OS that was better with four to eight cycles of DS therapy than with one to three cycles of DS therapy, with the best 5-year OS of 77.4% (95% confidence interval, 66.5-90.1%) for eight cycles. The 5-year DFS was approximately 66% when four or eight cycles of DS therapy were given. CONCLUSION: Although eight cycles of DS therapy may prolong prognosis, the present study did not provide a clear conclusion as to how many DS therapy cycles are needed to improve prognosis after D2 gastrectomy for stage III gastric cancer. TRIAL REGISTRATION: Registration number: UMIN00000714 and UMIN000004440.
Assuntos
Neoplasias Gástricas , Humanos , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/cirurgia , Neoplasias Gástricas/patologia , Docetaxel/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Tegafur/uso terapêutico , Quimioterapia Adjuvante , Gastrectomia , Estadiamento de NeoplasiasRESUMO
PURPOSE: The goal of the current study was to identify prognostic factors for disease-free survival (DFS) and overall survival (OS) in high-risk stage II colon cancer. METHODS: The subjects were patients with histologically confirmed stage II colon cancer undergoing R0 resection who met at least one of the following criteria: T4, perforation/penetration, poorly differentiated adenocarcinoma, mucinous carcinoma, and < 12 examined lymph nodes. Patients self-selected surgery alone or a 6-month oral uracil and tegafur plus leucovorin (UFT/LV) regimen. Serum CEA mRNA at ≥ 24 h after surgery and < 2 weeks after registration was also examined as a potential prognostic factor for stage II colon cancer. This study is registered with UMIN-CTR (protocol ID: UMIN000007783). RESULTS: 1880 were included in the analysis to identify prognostic factors for DFS and OS in patients with high-risk stage II colon cancer. In multivariate analyses, gender, depth of tumor invasion, extent of lymph node dissection, number of examined lymph nodes, and postoperative adjuvant chemotherapy (POAC) emerged as significant independent prognostic factors for DFS. Similarly, multivariate analysis showed that age, gender, depth of tumor invasion, perforation/penetration, extent of lymph node dissection, number of examined lymph nodes, and POAC were significant independent prognostic factors for OS. Univariate analyses showed no significant difference in DFS or OS for CEA mRNA-positive and mRNA-negative cases. CONCLUSION: This study showed that gender, depth of tumor invasion, extent of lymph node dissection, number of examined lymph nodes, and lack of use of POAC were significant independent prognostic factors in stage II colon cancer.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias do Colo , Humanos , Prognóstico , Estadiamento de Neoplasias , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/cirurgia , Tegafur/uso terapêutico , Quimioterapia Adjuvante , RNA Mensageiro/uso terapêutico , Estudos RetrospectivosRESUMO
Prof. Setsuro Fujii achieved significant results in the field of drug discovery research in Japan. He developed nine well-known drugs: FT, UFT, S-1 and FTD/TPI are anticancer drugs, while cetraxate hydrochloride, camostat mesilate, nafamostat mesilate, gabexate mesilate and pravastatin sodium are therapeutic drugs for various other diseases. He delivered hope to patients with various diseases across the world to improve their condition. Even now, drug discovery research based on Dr. Fujii's ideas is continuing.
Assuntos
Antineoplásicos , Gabexato , Masculino , Humanos , Pirimidinas , Gabexato/uso terapêutico , Antineoplásicos/uso terapêutico , Tegafur/uso terapêutico , Japão , UracilaRESUMO
Although adjuvant tegafur/uracil (UFT) is recommended for patients with completely resected stage I non-small-cell lung cancer (NSCLC) in Japan, only one-third of cases has received adjuvant chemotherapy (ADJ) according to real-world data. Therefore, robust predictive biomarkers for selecting ADJ or observation (OBS) without ADJ are needed. Patients who underwent complete resection of stage I lung adenocarcinoma with or without adjuvant UFT were enrolled. The status of ACTN4 gene amplification was analyzed by FISH. Statistical analyses to determine whether the status of ACTN4 gene amplification affected recurrence-free survival (RFS) were carried out. Formalin-fixed, paraffin-embedded samples from 1136 lung adenocarcinomas were submitted for analysis of ACTN4 gene amplification. Ninety-nine (8.9%) of 1114 cases were positive for ACTN4 gene amplification. In the subgroup analysis of patients aged 65 years or older, the ADJ group had better RFS than the OBS group in the ACTN4-positive cohort (hazard ratio [HR], 0.084, 95% confidence interval [CI], 0.009-0.806; P = .032). The difference in RFS between the ADJ group and the OBS group was not significant in ACTN4-negative cases (all ages: HR, 1.214; 95% CI, 0.848-1.738; P = .289). Analyses of ACTN4 gene amplification contributed to the decision regarding postoperative ADJ for stage I lung adenocarcinomas, preventing recurrence, improving the quality of medical care, preventing the unnecessary side-effects of ADJ, and saving medical costs.
Assuntos
Actinina/genética , Adenocarcinoma de Pulmão/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Tegafur/uso terapêutico , Uracila/uso terapêutico , Adenocarcinoma de Pulmão/genética , Adenocarcinoma de Pulmão/patologia , Adenocarcinoma de Pulmão/cirurgia , Idoso , Biomarcadores Tumorais/genética , Quimioterapia Adjuvante , Feminino , Amplificação de Genes , Humanos , Japão , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/cirurgia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Estudos Retrospectivos , Resultado do TratamentoRESUMO
OBJECTIVE: To investigate the efficacy and safety of additional S-1 chemotherapy to S-1 plus oxaliplatin (SOX) regimen chemotherapy for Stage III gastric carcinoma (GC) after radical resection. PATIENTS AND METHODS: A total of 161 patients who were pathologically diagnosed as Stage III GC after D2 gastrectomy and received SOX regimen adjuvant chemotherapy between January 2012 and April 2016 were included in this retrospective study. SOX regimen postoperative chemotherapy was composed of Oxaliplatin and S-1, administrated every 3 weeks for 8 scheduled courses. After SOX chemotherapy, 76 patients preferred additional chemotherapy with S-1 (the ACT group), while additional S-1 chemotherapy was not given to the other 85 patients (control group). The ACT with S-1 was administrated every 3 weeks for 8 scheduled courses. Treatment was terminated in case of life-threatening adverse events or tumor progression, or patients' demand for termination. Progression-free survival (PFS), overall survival (OS), and adverse events were analyzed. RESULTS: ACT group obtained markedly improved 3-year PFS [p = 0.04; hazard ratio (HR) for disease progression, 0.58; 95% confidence interval (CI), 0.34-0.98] and OS than the control group (p = 0.0469; HR for death, 0.56; 95% CI, 0.32-0.99). No chemotherapy-related mortality occurred. Patients of the ACT group suffered more common and severer hand-foot syndrome (HFS) (p = 0.02). CONCLUSIONS: Additional S-1 chemotherapy may be helpful for improving the disease progression and survival for patients with Stage III GC after radical resection with an acceptable safety profile.
Assuntos
Antimetabólitos Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Oxaliplatina/uso terapêutico , Ácido Oxônico/uso terapêutico , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/cirurgia , Tegafur/uso terapêutico , Antimetabólitos Antineoplásicos/farmacologia , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Combinação de Medicamentos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Oxaliplatina/farmacologia , Ácido Oxônico/farmacologia , Intervalo Livre de Progressão , Estudos Retrospectivos , Neoplasias Gástricas/mortalidade , Tegafur/farmacologiaRESUMO
BACKGROUND: To compare the prognosis of first-line systemic chemotherapy of AS (Albumin-bound paclitaxel and S-1) versus SOX (S-1 and oxaliplatin) regimen in Chinese gastric cancer patients with peritoneal metastasis. METHODS: This was a real-world study of gastric cancer patients with peritoneal metastasis who have been treated with AS or SOX regimen as first-line chemotherapy. Patients were matched by the method of propensity score matching (PSM). The primary and secondary endpoints were overall survival (OS) and progress-free survival (PFS). RESULTS: A total of 108 gastric cancer patients with peritoneal metastasis were enrolled after PSM analysis. There was no significant difference between AS and SOX regimen based on gender, age, ascites, treatment cycles, gastric cancer resection, received checkpoint inhibitors, and HER-2 expression after PSM analysis. The median OS (14.13 vs. 11.17 months, p = 0.0356) and median PFS (10.30 vs. 6.70 months, p = 0.0003) of patients who received AS regimen were longer than those treated by SOX regimen as first-line systemic chemotherapy. In sub-group analysis, the median OS and median PFS were longer for patients in AS regimen than SOX regimen in Lauren diffuse type. The occurrence of toxicity between the two groups was shown no significant difference. CONCLUSIONS: The results verified that AS regimen was more effective than SOX chemotherapy in gastric cancer patients with peritoneal metastasis, especially in Lauren diffuse type.
Assuntos
Neoplasias Peritoneais , Neoplasias Gástricas , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Combinação de Medicamentos , Gastrectomia , Humanos , Oxaliplatina/uso terapêutico , Ácido Oxônico/uso terapêutico , Neoplasias Peritoneais/tratamento farmacológico , Neoplasias Peritoneais/etiologia , Neoplasias Peritoneais/cirurgia , Neoplasias Gástricas/patologia , Tegafur/uso terapêuticoRESUMO
Background and Objectives: Postoperative adjuvant therapy with uracil and tegafur (UFT) is often used for stage II colon cancer in Japan, but a limited number of studies have investigated the effects of UFT in these patients. Materials and Methods: We conducted a population-based cohort study in patients with resected stage II colon cancer comparing the outcomes after postoperative adjuvant chemotherapy with UFT with an observation-only group. The data were collected from the Taiwan National Health Insurance Research Database from 2000 to 2015. The outcomes of the study were disease-free survival (DFS) and overall survival (OS). The hazard ratios (HRs) were calculated using multivariate Cox proportional hazard regression models. Results: No differences in the DFS and OS were detected between the UFT (1137 patients) and observation (2779 patients) cohorts (DFS: adjusted HR 0.702; 95% confidence interval (CI) 0.489-1.024; p = 0.074) (OS: adjusted HR 0.894; 95% CI 0.542-1.186; p = 0.477). In the subgroup analyses of the different substages, UFT prolonged DFS in patients with stage IIA colon cancer (adjusted HR 0.652; 95% CI 0.352-0.951; p = 0.001) compared with DFS in the observation cohort, but no differences in the OS were detected (adjusted HR 0.734; 95% CI 0.475-1.093; p = 0.503). Conclusions: Our results show that DFS improved significantly in patients with stage IIA colon cancer receiving UFT as a postoperative adjuvant chemotherapy compared with DFS in the observation group.
Assuntos
Neoplasias do Colo , Tegafur , Humanos , Tegafur/uso terapêutico , Uracila/uso terapêutico , Estudos de Coortes , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Estadiamento de Neoplasias , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/cirurgia , Quimioterapia Adjuvante , Intervalo Livre de DoençaRESUMO
A 78-year-old man was diagnosed with HER2-positive advanced gastric cancer, cT3N2M1(LYM: #16a1, 16b1), cStage â £B, after being referred for anemia. The lesion was deemed unresectable, and first-line chemotherapy was initiated using S-1, cisplatin(CDDP), and trastuzumab(T-mab). After 2 courses of chemotherapy, the patient developed febrile neutropenia( Grade 3). At this point, the lesion showed partial response(PR), and chemotherapy was continued using oral S-1 as a single agent. After 3 months of S-1 monotherapy, the para-aortic lymph node metastases showed a complete response (CR). S-1 monotherapy was continued without major adverse events for 2 years, and the patient is presently alive and well 6 years after obtaining clinical CR. This may suggest that S-1 is a safe and effective treatment for unresectable advanced gastric cancer in elderly patients.
Assuntos
Neoplasias Gástricas , Masculino , Humanos , Idoso , Neoplasias Gástricas/cirurgia , Cisplatino/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Tegafur/uso terapêutico , Trastuzumab/uso terapêutico , Linfonodos/patologia , Combinação de Medicamentos , GastrectomiaRESUMO
We report a cases report of colorectal cancer who underwent repeated resection for peritoneal recurrences by laparoscopic surgery. In 2013, a 70-year-old woman diagnosed with an ascending colon cancer underwent laparoscopic right hemicolectomy. The pathological diagnosis was tub2, pT4aN1M0, Stage â ¢b. Postoperative adjuvant chemotherapy(uracil and tegafur/Leucovorin)was administered. PET-CT performed at 25 months after the surgery because of CEA elevation. It revealed a peritoneal recurrence in the pouch of Douglas. The following peritoneal recurrences were removed by laparoscopic Hartmann's procedure. Chemotherapy(5-fluorouracil/levofolinate/oxaliplatin/bevacizumab)was administered 11 courses and after that chemotherapy(5-fluorouracil/levofolinate/bevacizumab)was administered 6 courses. PET-CT performed 37 months after the second surgery revealed a peritoneal recurrence near the right ovary in the pouch of Douglas. The following peritoneal recurrences was removed. Chemotherapy(tegafur/gimeracil/oteracil/bevacizumab)was administered 11 courses. The long-term survival has been continued for 7 years and 7 months after first operation. It was considered that laparoscopic surgery for peritoneal recurrence in colorectal cancer is contributed to one of the surgical procedures in selected patients.
Assuntos
Neoplasias do Colo , Neoplasias Colorretais , Laparoscopia , Neoplasias Peritoneais , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bevacizumab/uso terapêutico , Neoplasias do Colo/cirurgia , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/patologia , Neoplasias Colorretais/cirurgia , Feminino , Fluoruracila/uso terapêutico , Humanos , Leucovorina/uso terapêutico , Neoplasias Peritoneais/tratamento farmacológico , Neoplasias Peritoneais/cirurgia , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Recidiva , Tegafur/uso terapêuticoRESUMO
LESSONS LEARNED: Because S-1 is orally administered, OX-IRIS does not necessitate the continuous infusion of 5-FU and is more convenient. The recommended dose of OX-IRIS was determined to be level -1 (oxaliplatin, 65 mg/m2 ; irinotecan, 100 mg/m2 ; S-1, 80 mg/m2 ), which has manageable safety and promising anticancer activities. BACKGROUND: OX-IRIS is a new combination therapy of oxaliplatin, irinotecan, and S-1 for unresectable pancreatic ductal adenocarcinoma (PDAC), which may be beneficial because S-1 is administered orally and continuous infusion of 5-fluorouracil (5-FU) is not needed. METHODS: Patients who had not received prior therapy for unresectable PDAC were enrolled. Adenocarcinoma or adenosquamous histology was required. Oxaliplatin and irinotecan were administered on days 1 and 15; S-1 was administered orally twice a day on days 1-14, followed by 14 days of rest (one cycle). Primary endpoints were dose-limiting toxicity (DLT) and maximum tolerated dose (MTD). Secondary endpoints were safety, overall response rate (ORR), progression-free survival (PFS), and overall survival (OS). RESULTS: In level 0 (oxaliplatin, 85 mg/m2 ; irinotecan, 100 mg/m2 ; S-1, 80 mg/m2 ), two of five patients experienced DLT. In level -1 (oxaliplatin, 65 mg/m2 ; irinotecan, 100 mg/m2 ; S-1, 80 mg/m2 ), DLT could not be evaluated in two of eight patients because one cycle was not completed; one of the remaining six patients experienced DLT. Anemia, thrombocytopenia, fatigue, nausea, anorexia, diarrhea, and peripheral sensory neuropathy were seen frequently in levels 0 and -1. ORR was 30% in levels 0 and -1. Median progression-free survival and median overall survival were 4.1 months (95% confidence interval [CI], 0.0-8.9 months) and 13.7 months (95% CI, 4.8-22.6 months), respectively. CONCLUSION: MTD of OX-IRIS therapy was estimated to be level 0, and the recommended dose (RD) for future trial was level -1.